Aspiration of conjugated bile acids predicts adverse lung transplant outcomes and correlates with airway lipid and cytokine dysregulation.

INTRODUCTION: Duodeno-gastroesophageal reflux aspiration is associated with chronic lung allograft dysfunction (CLAD). Reflux aspirate can contain bile acids (BA), functional molecules in the gastro-intestinal tract with emulsifying properties. We sought to determine and quantify the various BA species in airways of the lung transplant recipients to better understand the various effects of aspirated BA that contribute to post-transplantation outcomes. METHODS: Bronchial washings (BW) were prospectively collected from lung transplant recipients and subsequently assayed by liquid chromatography-mass spectrometry for 13 BA and 25 lipid families. Patients were monitored for CLAD, rejection, inflammation and airway infections. RESULTS: Detectable BA were present in 45/50 patients (90%) at 3 months after transplant. Elevated BA and predominance of conjugated species were independent predictors of CLAD (hazard ratio 7.9; 95% confidence interval 2.7-23.6; p < 0.001 and 7.3; 2.4-22; p < 0.001, respectively) and mortality (hazard ratio 4.4; 1.5-12.7; p = 0.007 and 4.8; 1.4-15.8; p = 0.01, respectively). High BA associated with increased positive bacterial cultures (60% vs 25%, p = 0.02). Primary conjugated species independently correlated with the rate of bacterial cultures during the first-year post-transplant (Beta coefficient: 0.77; 0.28-1.26; p = 0.003) and changes in airway lipidome and cytokines. CONCLUSIONS: Higher BA levels and predominance of conjugated BA are independent predictors of chronic lung allograft dysfunction, mortality and bacterial infections. Primary conjugated BA are related to distinct changes in airway lipidome and inflammatory cytokines. This elucidates novel evidence into the mechanism following BA aspiration and proposes novel markers for prediction of adverse post-transplant outcomes.

Right single lung transplantation or double lung transplantation compared with left single lung transplantation in chronic obstructive pulmonary disease.

BACKGROUND: Although single and double lung transplantation outcomes for chronic obstructive pulmonary disease (COPD) have been investigated, right and left single lung transplants have never been rigorously compared to evaluate disease-specific differences. Single lung transplants for COPD often have hyperinflation of the contralateral native lung, which may be more pronounced in left lung transplants. METHODS: Using the United Network for Organ Sharing registry, we conducted a retrospective cohort study of 5,585 adults who underwent lung transplantation for COPD from May 4, 2005 to June 30, 2017. Subjects were followed until March 2019. Post-transplant survival was compared using Cox proportional hazards and Royston and Parmar's flexible parametric survival models. We adjusted for donor and recipient factors with known or plausible associations with survival. RESULTS: Lung transplant recipients who received a left single lung transplant for COPD had an increased risk of post-transplant death when compared with those who received a right single lung transplant for COPD (hazard ratio [HR]: 1.24, 95% CI: 1.08-1.48, p = 0.002). Survival did not differ significantly between double lung transplant and right single lung transplant recipients (HR: 0.88, 95% CI: 0.77-1.02, p = 0.086). Adjusted 5-year survival was 57.8% (95% CI: 55.7-60.1) for double lung recipients, 56.7% (95% CI: 55.4-58.0) for right single lung recipients, and 50.9% (95% CI: 47.2-55.0) for left single lung recipients. CONCLUSIONS: In COPD, right single lung transplantation was associated with improved post-transplant survival compared with left single lung transplantation, and no significant difference in post-transplant survival compared with double lung transplantation was found. In light of the ongoing donor lung shortage, preferential allocation of right single lungs to patients with COPD should be considered.

Geographic disparities in donor lung supply and lung transplant waitlist outcomes: A cohort study.

Despite the Final Rule mandate for equitable organ allocation in the United States, geographic disparities exist in donor lung allocation, with the majority of donor lungs being allocated locally to lower-priority candidates. We conducted a retrospective cohort study of 19 622 lung transplant candidates waitlisted between 2006 and 2015. We used multivariable adjusted competing risk survival models to examine the relationship between local lung availability and waitlist outcomes. The primary outcome was a composite of death and removal from the waitlist for clinical deterioration. Waitlist candidates in the lowest quartile of local lung availability had an 84% increased risk of death or removal compared with candidates in the highest (subdistribution hazard ratio [SHR]: 1.84, 95% confidence interval [CI]: 1.51-2.24, P < .001). The transplantation rate was 57% lower in the lowest quartile compared with the highest (SHR: 0.43, 95% CI: 0.39-0.47). The adjusted death or removal rate decreased by 11% with a 50% increase in local lung availability (SHR: 0.89, 95% CI: 0.85-0.93, P < .001) and the adjusted transplantation rate increased by 19% (SHR: 1.19, 95% CI: 1.17-1.22, P < .001). There are geographically disparate waitlist outcomes in the current lung allocation system. Candidates listed in areas of low local lung availability have worse waitlist outcomes.

Malignancies following lung transplantation.

Malignancy is an important complication of thoracic organ transplantation and is associated with significant morbidity and mortality. Lung transplant recipients are at greater risk for cancer than immunocompetent persons, with cancer-specific incidence rates up to 60-fold higher than the general population. The increased risk for cancer is attributed to neoplastic properties of immunosuppressive medications, oncogenic viruses, and cancer-specific risk factors. This article addresses the epidemiology, presentation, and treatment of the most common malignancies after lung transplantation, including skin cancer, posttransplant lymphoproliferative disorder, and bronchogenic carcinoma.